AD: VD levels in the brain are very important! The first quantitative study found that a doubling of vitamin D levels in the brain was associated with a 33% lower risk of dementia or mild cognitive impairment

*For medical professionals only

Available data show that by 2050, the incidence of dementia in the world will exceed 150 million
.
This means that from now on, we need to think about and adopt more prevention strategies to deal with the social burden of Alzheimer's disease and other dementias [1].

In fact, some of the nutrients we consume in our daily lives play an important role in delaying cognitive decline, including fat-soluble vitamin D [2].

25-Hydroxyvitamin D 3 (25(OH)D₃) is the most dominant form of
vitamin D in the blood circulation.
Previous studies have shown that low vitamin D intake or low blood levels of 25(OH)D3 are associated with cognitive decline and dementia [3-4].

However, these studies were based
on dietary intake or blood levels of vitamin D.

To date, there have been no studies showing a specific relationship between vitamin D levels in the brain and cognitive decline, and whether circulating levels of 25(OH)_D3 reflect vitamin D levels
in the brain.

Recently, a research team led by Sarah L.
Booth of Tufts University published important research results in Alzheimer's & Dementia [5].

They found that higher levels of vitamin D in the brain were associated with a reduced risk of dementia or mild cognitive impairment.

Specifically, a 1-fold increase in brain 25(OH)D3 levels was associated with a 25% to₃₃% reduction in the incidence of dementia or mild cognitive impairment (P≤0.
031).

This finding also provides nutritional prevention strategies
for dementia and cognitive impairment.

Screenshot of the first page of the paper

Participants in the study were all from the Rush Memory and Aging Project (MAP) [6], a longitudinal research project
exploring the risk of developing Alzheimer's disease and its associated disorders.

Participants were recruited without dementia and required annual clinical blood tests and agreed to donate brain tissue for autopsy after death [7].

In this study, data from a total of 290 trial-eligible subjects were included in the analysis, 270 of whom were tested
for total plasma 25(OH)_D3 and vitamin D-binding protein (DBP) levels.

In circulation, 99% of 25(OH)_D3 is present in the bound state (mostly bound to DBP), and the remaining 1% is in the free state
.
Because free 25(OH)D is better utilized by some tissues, the researchers also included data from free 25(OH)D in the analysis
.

Subject data screening process

To better assess the relationship between vitamin D levels and cognitive function in the brain, the researchers screened four brain regions, the middle temporal cortex (MT), the middle and anterior cortex (MF), the cerebellum (CR), and the anterior watershed white matter (AWS), and then in autopsy samples, the four brain regions were given vitamin D, 25(OH)D3, 1,25-dihydroxyvitamin D₃ (1,25(OH)_D3 levels were tested and their association
with cognitive function was determined.

After linear correlation analysis, the researchers found that in the four brain regions, plasma total 25(OH)D3 and free 25(OH)D levels were positively correlated with brain 25(OH)_D3 levels (r=0.
32-0.
39 P≤0.
0001).

Total plasma 25(OH)D3 and free 25(OH)D are moderately positively correlated (i.
e.
, the two trends are consistent and can reflect each other's growth levels, r=0.
73, P≤0.
0001), which means that plasma total 25(OH)_D3 and free 25(OH) D levels can reflect 25(OH)_D3 levels
in the brain to some extent.

After comparing the results of the subjects' last cognitive test before death, the researchers found that a 1-fold increase in brain 25(OH)_D3 levels in four brain regions was associated with a 25 to 33 percent reduction in the incidence of dementia or mild cognitive impairment (OR, 0.
669-0.
754, P≤0.
031).

The amount of 25(OH)D in each brain region

This result is also consistent
with the subjects' final cognitive diagnosis.
Of all brain regions tested, the higher the level of 25(OH)_D3, the higher the subject's prenatal cognitive function test score (P≤0.
025).

In AWS brain regions in particular, having high levels of 25(OH)_D3 was found to delay the progression of cognitive impairment (β=0.
01, P=0.
044) and was associated with
better episodic memory and perceptual abilities.
However, the 25(OH)_D3 content of the brain has not been found to be associated with
Alzheimer's disease pathological markers (β amyloid, etc.
).

Plasma levels of 25(OH)_D3, free 25(OH)D, and DBP were not found to be associated with overall cognitive function or degree of cognitive decline (P>0.
06).

However, higher levels of plasma DBP were significantly associated with
slower semantic memory decline (P=0.
0046) and perceptually directed decline (P=0.
04).

The total content of 25(OH)_D3 in each brain region increased, and the degree of cognitive impairment decreased

This study is the first to quantitatively detect vitamin D in human brain tissue and explore its relationship with cognitive ability and neuropathology
.
Although the results suggest that brain 25(OH)D3 levels are associated with better semantic and working memory, this is not a basis for taking high-dose vitamin D supplements, and more research is needed to better understand the role of
vitamin D in delaying dementia or mild cognitive impairment.

References:

[1] GBD 2019 Dementia Forecasting Collaborators.
Estimation of the global prevalence of dementia in 2019 and forecasted prevalence in 2050: an analysis for the Global Burden of Disease Study 2019.
Lancet Public Health.
2022; 7(2):e105-e125.
doi:10.
1016/S2468-2667(21)00249-8

[2] Scarmeas N, Anastasiou CA, Yannakoulia M.
Nutrition and prevention of cognitive impairment.
Lancet Neurol.
2018; 17(11):1006-1015.
doi:10.
1016/S1474-4422(18)30338-7

[3] Buell JS, Dawson-Hughes B, Scott TM, et al.
25-Hydroxyvitamin D, dementia, and cerebrovascular pathology in elders receiving home services.
Neurology.
2010; 74(1):18-26.
doi:10.
1212/WNL.
0b013e3181beecb7

[4] Beydoun MA, Hossain S, Fanelli-Kuczmarski MT, et al.
Vitamin D Status and Intakes and Their Association With Cognitive Trajectory in a Longitudinal Study of Urban Adults.
J Clin Endocrinol Metab.
2018; 103(4):1654-1668.
doi:10.
1210/jc.
2017-02462

[5] Shea MK, Barger K, Dawson-Hughes B, et al.
Brain vitamin D forms, cognitive decline, and neuropathology in community-dwelling older adults [published online ahead of print, 2022 Dec 7].
Alzheimers Dement.
2022; 10.
1002/alz.
12836.
doi:10.
1002/alz.
12836

[6] Bennett DA, Schneider JA, Buchman AS, Barnes LL, Boyle PA, Wilson RS.
Overview and findings from the rush Memory and Aging Project.
Curr Alzheimer Res.
2012; 9(6):646-663.
doi:10.
2174/156720512801322663

[7] Bennett DA, Schneider JA, Buchman AS, Mendes de Leon C, Bienias JL, Wilson RS.
The Rush Memory and Aging Project: study design and baseline characteristics of the study cohort.
Neuroepidemiology.
2005; 25(4):163-175.
doi:10.
1159/000087446

Responsible editorZhang Jinxu